DUBLIN--(BUSINESS WIRE)--Alkermes plc (NASDAQ: ALKS) today announced positive preliminary topline results from ENLIGHTEN-1, the first of two key phase 3 studies in the ENLIGHTEN clinical development program for ALKS 3831, an investigational, novel, once-daily, oral atypical antipsychotic drug candidate for the treatment of schizophrenia. ENLIGHTEN-1 was a multinational, double-blind, randomized, phase 3 study that evaluated the antipsychotic efficacy, safety and tolerability of ALKS 3831 compared to placebo over four weeks in 403 patients experiencing an acute exacerbation of schizophrenia. The study also included a comparator arm of olanzapine, an established atypical antipsychotic agent with proven efficacy. The study met the prespecified primary endpoint, with ALKS 3831 demonstrating statistically significant reductions from baseline in Positive and Negative Syndrome Scale (PANSS) scores compared to placebo (p<0.001). Data from the study also showed that olanzapine achieved similar improvements from baseline PANSS scores, compared to placebo (p=0.004). The study also met its key secondary endpoint of improvement on the Clinical Global Impression – Severity (CGI-S) scale for ALKS 3831 versus placebo (p=0.002). ALKS 3831 is designed to provide the strong antipsychotic efficacy of olanzapine and a differentiated safety profile with favorable weight and metabolic properties.
“The positive results of ENLIGHTEN-1 provide clear evidence of the safety, tolerability and antipsychotic efficacy of ALKS 3831 in a large, randomized registration trial,” said Elliot Ehrich, M.D., Executive Vice President of Research and Development at Alkermes. “The results of this phase 3 study also provide additional evidence of the antipsychotic properties of ALKS 3831 relative to olanzapine, an agent well known to clinicians. We look forward to completing our analysis of this large study and presenting the data at a future medical meeting.”
“Many physicians recognize the powerful efficacy profile of olanzapine, but are hesitant to prescribe it given the severe weight gain and metabolic side effects commonly associated with its use,” said Christoph Correll, M.D., Professor of Psychiatry and Molecular Medicine at Hofstra Northwell School of Medicine. “A new antipsychotic with robust efficacy and a favorable weight and metabolic profile compared to olanzapine would be a welcome addition to the schizophrenia treatment landscape. This study confirms a key element of this profile, with a clear demonstration of efficacy in a large, well-conducted clinical trial.”
Overall, 91% of patients who received ALKS 3831 completed the study, compared to 89% of patients who received olanzapine and 83% of patients who received placebo. The most common adverse events for both the ALKS 3831 and olanzapine treatment groups were weight gain, somnolence and dry mouth.
Alkermes will present comprehensive data from the ENLIGHTEN-1 study at an upcoming medical meeting and submit the results for publication in a peer-reviewed journal. ENLIGHTEN-2, a six-month phase 3 study evaluating the weight gain profile of olanzapine compared to ALKS 3831, is ongoing with data expected in 2018.
About the ENLIGHTEN-1 Study
ENLIGHTEN-1
was a multinational, double-blind, randomized, phase 3 study that
evaluated the antipsychotic efficacy, safety and tolerability of ALKS
3831 compared to placebo over four weeks in patients experiencing an
acute exacerbation of schizophrenia. The study also included a
comparator arm of olanzapine, an established atypical antipsychotic
agent with proven efficacy but also metabolic liabilities, including
significant weight gain.1 The trial included adult patients
who met the Diagnostic and Statistical Manual of Mental Disorders –
Fifth Edition criteria for schizophrenia, and had a PANSS score of
80 or higher at study baseline.
A total of 403 patients were randomized in a 1:1:1 manner to receive once-daily, oral tablets of ALKS 3831, olanzapine or placebo for four weeks. Patients randomized to the ALKS 3831 treatment group received a bilayer fixed-dose tablet of 10 mg samidorphan co-formulated with either 10 or 20 mg of olanzapine. Patients randomized to the olanzapine treatment group received either 10 or 20 mg of olanzapine. The primary efficacy endpoint of the study was the mean change from baseline at Week 4 in PANSS total score for ALKS 3831 compared to placebo, using a Mixed Model with Repeated Measurements (MMRM) model. The key secondary endpoint of the study was change from baseline in the CGI-S score at Week 4.
All participants who completed the double-blind portion of the study were eligible to continue in an open-label, long-term safety study and receive ALKS 3831 for an additional 12 months. The objective of the extension phase of the study is to assess the long-term safety, tolerability and durability of effect of ALKS 3831.
Conference Call
Alkermes will
host a conference call today, June 29, 2017, at 4:30 p.m. ET (9:30 p.m.
BST), to discuss these topline results. The conference call may be
accessed by dialing +1 888 424 8151 for U.S. callers and +1 847 585 4422
for international callers. The conference call ID number is 6037988. The
conference call will also be webcast on the Investors section of
Alkermes’ website at www.alkermes.com.
The webcast will be archived on the Investors section of the Alkermes
website for at least 90 days.
About the ENLIGHTEN Clinical Development Program
The
ENLIGHTEN clinical development program for ALKS 3831 is comprised of two
key studies: a study evaluating the antipsychotic efficacy of ALKS 3831
compared to placebo over four weeks and a study assessing weight gain
with ALKS 3831 compared to olanzapine in patients with schizophrenia
over six months. The program also includes supportive studies to
evaluate the pharmacokinetic and metabolic profile of ALKS 3831, the
effect on body weight of ALKS 3831 in young adult patients early in
their illness, and long-term safety.
About ALKS 3831
ALKS 3831 is a
proprietary, investigational medicine designed as a broad-spectrum
antipsychotic for the treatment of schizophrenia. ALKS 3831 is composed
of samidorphan, a novel, new molecular entity co-formulated with the
established antipsychotic agent, olanzapine, in a single bilayer tablet.
Weight gain is a common and clinically relevant metabolic side effect of atypical antipsychotic medications, and olanzapine, commercially available as ZYPREXA®, has one of the highest incidences and greatest amounts of weight gain among the widely prescribed products in this class of drugs.1 ALKS 3831 is designed to provide the strong antipsychotic efficacy of olanzapine and a differentiated safety profile with favorable weight and metabolic properties.
About Schizophrenia
Schizophrenia
is a chronic, severe and disabling brain disorder. The disease is marked
by positive symptoms (hallucinations and delusions) and negative
symptoms (depression, blunted emotions and social withdrawal), as well
as by disorganized thinking. An estimated 2.4 million American adults
have schizophrenia,2 with men and women affected equally.
About Alkermes
Alkermes plc is
a fully integrated, global biopharmaceutical company developing
innovative medicines for the treatment of central nervous system (CNS)
diseases. The company has a diversified commercial product portfolio and
a substantial clinical pipeline of product candidates for chronic
diseases that include schizophrenia, depression, addiction and multiple
sclerosis. Headquartered in Dublin, Ireland, Alkermes plc has an R&D
center in Waltham, Massachusetts; a research and manufacturing facility
in Athlone, Ireland; and a manufacturing facility in Wilmington, Ohio.
For more information, please visit Alkermes’ website at www.alkermes.com.
Note Regarding Forward-Looking Statements
Certain
statements set forth in this press release constitute “forward-looking
statements” within the meaning of the Private Securities Litigation
Reform Act of 1995, as amended, including, but not limited to,
statements concerning: the timing of receipt and reporting of the phase
1 metabolic and ENLIGHTEN-2 study results; and the therapeutic value,
development plans and commercial potential of ALKS 3831. You are
cautioned that forward-looking statements are inherently uncertain.
Although the company believes that such statements are based on
reasonable assumptions within the bounds of its knowledge of its
business and operations, the forward-looking statements are neither
promises nor guarantees and they are necessarily subject to a high
degree of uncertainty and risk. Actual performance and results may
differ materially from those expressed or implied in the forward-looking
statements due to various risks and uncertainties. These risks and
uncertainties include, among others: whether preclinical and clinical
results for ALKS 3831 will be predictive of future clinical study
results; whether the ENLIGHTEN-2 study for ALKS 3831 will be completed
on time or at all; potential changes in cost, scope and duration of the
ALKS 3831 clinical development program; whether ALKS 3831 could be shown
ineffective or unsafe during clinical studies; and those risks and
uncertainties described under the heading “Risk Factors” in the
company’s Annual Report on Form 10-K for the year ended Dec. 31, 2016
and Quarterly Report on Form 10-Q for the quarter ended Mar. 31, 2017
and in subsequent filings made by the company with the U.S. Securities
and Exchange Commission (SEC), which are available on the SEC’s website
at www.sec.gov.
Existing and prospective investors are cautioned not to place undue
reliance on these forward-looking statements, which speak only as of the
date hereof. Except as required by law, the company disclaims any
intention or responsibility for updating or revising any forward-looking
statements contained in this press release.
ZYPREXA® is a registered trademark of Eli Lilly & Company.
1Komossa, K. et al. Olanzapine versus other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews. 2010, Issue 3. Art. No.: CD006654.
2National Institutes of Health. Schizophrenia. Accessed on June 29, 2017 from http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=67&key=S#S.
